Haemolytic uraemic syndrome Flashcards
Define haemolytic uraemic syndrome.
Haemolytic uraemic syndrome (HUS) is characterised by the triad of :
- microangiopathic haemolytic anaemia,
- thrombocytopenia,
- AKI
What are the two forms of haemolytic uraemic syndrome?
- D+ (diarrhoea-associated fomr)
- D- (no prodromal illness identified)
How is HUS related to TTP?
HUS overlaps with thrombotic thrombocytopenia purpura (TTP), which has the additional features of fever and fluctuating CNS signs.
What are the risk factors for HUS?
- Ingestion of contaminated food or water
- Known community outbreak of toxicogenic E.coli
- Exposure to infected individuals in institutional setting
- Genetic predisposition (atypical HUS seen in familial syndromes and some sporadic cases)
Other:
- Bone marrow transplant
- Exposure to ciclosporin, some chemotherapy agents, targeted cancer agents, quinine
- Pregnancy- or postpartum-related - typically seen in primiparas who present at a median of 27 days post-delivery, but can be difficult to distinguish from other causes of thrombocytopenia
What is the pathophysiology of haemolytic uraemic syndrome?
An aetiological factor causes endothelial injury in the glomerular capillary bed → platelet aggregation and activation of platelets and the clotting cascade
This causes small vessel thrombosis which undergo fibrinoid necrosis. This also causes microangiopathic haemolytic anaemia and thrombocytopenia. This is followed by renal ischaemia and AKI.
Other organs such as the heart, intestine, and pancreas, and the central nervous system, may occasionally be affected due to microvascular thrombosis
List 3 causes of haemolytic uraemic syndrome.
Infection - Shiga toxin-producing E.coli(from contaminated water, dairy, meat), Shigella, neuraminidase-producing infections (e.g. pneumococcal RTI), HIV
Drugs - oral contraceptive pill, ciclosporin, mytomycin, 5-fluorouracil,
Others - malignant hypertension, malignancy, pregnancy, SLE, scleroderma, bone marrow transplant, pregnancy
What is the epidemiology of HUS? Who is most affected?
- Small clusters of sporadic outbreaks
- D+ HUS often affects young children (<5yrs), occurs more commonly in summer epidemics and is the most common cause of AKI in children
- Onset usually 5-10 days after diarrhoea onset
- 15% of children with STEC will have HUS features
What are the symptoms of HUS?
GI - severe abdominal colic, water diarrhoea that becomes bloodstained
General - malaise, fatigue, nausea, fever <38oC (D+ form)
Renal - oliguria or anuria, haematuria
What are the signs of HUS?
General - pallor (from anaemia), slight jaundice (from haemolysis), bruising (severe thrombocytopenis), generalised oedema, hypertension and retinopathy
GI - abdominal tenderness
CNS - especially in TTP (weakness, reduced vision, fits, reduced consciousness)
What investigations would you do for HUS?
Bloods -
- FBC - normocytic anaemia, thrombocytopenia, high neutrophils
- Blood film - schistocytes (= thrombotic micronagiopathy) , high reticulocytes, spherocytes.
- U&E - high urea, high creatinine, high urate
- Serum electrolytes - high K+; low Na+
- LDH - increased as RBC destroyed
- Haptoglobin - decreased (binds free Hb released by haemolysed RBC and gets absorbed by liver and spleen)
- Other:
- Clotting - normal unless DIC
- LFTs - high unconjugated bil, high LDH from haemolysis
- Blood cultures/PCR for Shiga toxin 1/2
- ABG - acidosis due to low bicar; low PaCO2, normal anion gap
Urine - haematuria, proteinuria
Stool samples - for PCR or culture for shiga toxin or STEC respectively
What invasive test can be done in cases of diagnostic doubt?
Renal biopsy - C/I in severe thrombocytopaenia. In cases of diagnostic doubt:
- D+ -arteriolar necrosis, glomerular capillary thrombosis
- D- - intimal proliferation in arterioles
What is the management of HUS?
Refer to haematology/nephrology
Admit to hospital
Fluids - reduces risk of oliguric AKI
+/- BB/CCB - treat hypertension, ACEi not recommended due to concerns over perfusion
+/- RBC transfusion - if severe anaemia
+/- Dialysis - in severe AKI
+/- Plasma exchange - for severe cases not associated with diarrhoea
+/- Eculizumab (C5 inhibitor mAb) - better than plasma exchange alone
+/- Renal transplant - if ESRF develops
Antibiotics have no role. Also avoid anti-diarrhoeals and NSAIDs.
Is HUS MAHA Coombs’ positive or negative?
Negative
Which E coli specifically commonly cause HUS?
Shiga toxin producing E coli (STEC) 0157:H7 (90% of cases)
What is meant by primary and secondary HUS?
Primary = due to complement dysregulation
Secondary = most common; due to extrinsic cause
